Aging and the mitochondrial response to exercise training, measured by noninvasive 31P magnetic resonance spectroscopy

通过无创 31P 磁共振波谱测量衰老和线粒体对运动训练的反应

基本信息

批准号：
10417265
负责人：
OWEN T. CARMICHAEL
金额：
$ 61.05万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10417265
关键词：
Acute Address Adult Aerobic Aerobic Exercise Age Aging Ancillary Study Attenuated Automobile Driving Bioenergetics Bioinformatics Biologic Characteristic Biological Biology Collaborations Collection DNA Methylation Data Disease Elderly Event Exercise Funding Health Health Benefit Individual Knowledge Light Link Magnetic Resonance Spectroscopy Measurement Measures Mitochondria Modality Molecular Molecular Profiling Multiomic Data Muscle Muscle Mitochondria Non-Insulin-Dependent Diabetes Mellitus Outcome Pathway interactions Persons Phenotype Phosphocreatine Physical Fitness Physical Function Physical activity Physiological Prevention Principal Investigator Proteomics Publishing Recovery Regulation Reporting Resistance Role Skeletal Muscle Technology Time Training Transducers United States National Institutes of Health VO2max Variant Work age group age related base cardiometabolism cardiorespiratory fitness clinically relevant epigenomics exercise prescription exercise training experience healthy aging improved in vivo inter-individual variation lipidomics member middle age mode of exercise muscular structure novel precision medicine programs resistance exercise response strength training transcriptomics vastus lateralis virtual young adult

项目摘要

Program Director/Principal Investigator (Last, First, Middle): Project Summary Reduced skeletal muscle mitochondrial oxidative capacity of skeletal muscle has been implicated in aging- related declines in cardiorespiratory fitness, physical functioning, and cardiometabolic health. Although exercise training in older adults increases mitochondrial capacity, virtually all of the data is reported in terms of average responses within groups. Yet within groups, there is enormous inter-individual variation in these responses. Two specific questions remain regarding the significance and implications of exercise-induced changes in mitochondrial capacity. 1) Does exercise improve mitochondrial capacity similarly in older and younger adults? 2) What are the molecular signatures within skeletal muscle that associate with improvements in mitochondrial capacity in older and younger adults? We will address these major gaps in knowledge by objectively assessing the spectrum of mitochondrial capacity responses to exercise in vivo, investigating the underlying molecular regulation of exercise responses, and relating the mitochondrial responses and molecular factors to clinically-relevant outcomes such as exercise-induced improvements in cardiorespiratory fitness (VO2max). The NIH-funded Molecular Transducers of Physical Activity Consortium (MoTrPAC) funds collection of comprehensive molecular signatures from biospecimens before and after 12 weeks of aerobic and resistance exercise training in healthy adults spanning the adult age span. This ancillary study will synergize with MoTrPAC and will add measurements of mitochondrial capacity of the skeletal muscle via non-invasive 31P magnetic resonance spectroscopy (31P-MRS) before and after training in 420 individuals across a wide age range (18 to 60+). Aim 1 is to assess differences in the mitochondrial capacity response to exercise training across the agespan and between aerobic and resistance training. Aim 2 is to identify molecular transducers of mitochondrial capacity induced by exercise. Primary hypotheses are that a proportion of individuals will not improve mitochondrial capacity following exercise training regardless of modality; age per se will not correlate with mitochondrial capacity responses; that greater improvements in mitochondrial capacity will associate similarly with greater improvements in cardiorespiratory fitness in younger and older adults; and that mitochondrial capacity responses will be greater with aerobic training compared to resistance training but aerobic-resistance differences will be similar across age groups. The impact of the project is that it will leverage the high-throughput `omics' technologies and exercise studies provided by MoTrPAC to shed light on mechanisms underlying the variation in mitochondrial capacity responses linked to health benefits of physical activity in older adults. OMB No. 0925-0001/0002 (Rev. 01/18 Approved Through 03/31/2020) Page Continuation Format Page

项目主任/首席研究员（最后、第一、中间）：项目概要骨骼肌线粒体氧化能力降低与衰老有关心肺健康、身体机能和心脏代谢健康的相关下降。虽然老年人的运动训练增加了线粒体的能力，几乎所有的数据都是用术语报告的组内的平均反应。然而，在群体内部，个体之间的这些差异却存在巨大的差异。回应。关于运动诱发的意义和影响，仍然存在两个具体问题线粒体容量的变化。 1) 运动是否同样可以提高老年人和老年人的线粒体能力？年轻人？ 2) 骨骼肌内与改善相关的分子特征是什么老年人和年轻人的线粒体能力如何？我们将通过以下方式解决这些主要的知识差距：客观评估线粒体能力对体内运动的反应范围，研究运动反应的潜在分子调节，以及将线粒体反应与分子影响临床相关结果的因素，例如运动引起的心肺健康改善（最大摄氧量）。 NIH 资助的身体活动分子传感器联盟 (MoTrPAC) 资助收集 12 周有氧运动前后生物样本的全面分子特征跨越成年年龄跨度的健康成年人的阻力运动训练。这项辅助研究将产生协同作用与 MoTrPAC 合作，将通过非侵入性方式添加骨骼肌线粒体容量的测量对 420 名不同年龄段的人进行训练前后的 31P 磁共振波谱 (31P-MRS) 范围（18 至 60+）。目标 1 是评估线粒体能力对运动训练反应的差异跨越年龄跨度以及有氧训练和阻力训练。目标 2 是识别分子传感器运动诱导的线粒体能力。主要假设是一部分人不会无论何种方式，运动训练后均可提高线粒体能力；年龄本身并不相关与线粒体容量反应；线粒体能力的更大改善将与同样，年轻人和老年人的心肺健康也有更大的改善；还有那个与阻力训练相比，有氧训练的线粒体能力反应会更大，但是不同年龄组的有氧阻力差异相似。该项目的影响是，它将利用 MoTrPAC 提供的高通量“组学”技术和运动研究来阐明与身体健康益处相关的线粒体能力反应变化的潜在机制老年人的活动。 OMB 编号 0925-0001/0002（修订版 01/18 批准至 03/31/2020）页面延续格式页面